Study on Biological Activity of Isoquinoline-Type Alkaloids

1. 异喹啉类生物碱的生物活性(1)原小檗碱型生物碱的细胞毒性利用人类肿瘤细胞系面板结合药物敏感性数据库，对与小檗碱相关的24种季系原小檗碱生物碱的细胞毒性活性进行了评价。在位置8或13延伸烷基链强烈影响细胞毒性活性，即相对亲脂性以及取代基的大小影响细胞毒性。在小檗碱的8-或13-己基取代衍生物中观察到最高水平的活性。(2)简单异喹啉类和苯基异喹啉类生物碱的生物活性对26种简单异喹啉类和21种苯基异喹啉类生物碱进行了抗菌、抗疟、细胞毒和抗hiv活性检测。一些简单的异喹啉生物碱在每种检测中都有显著的活性，可能是开发潜在化疗药物的先导化合物。异喹啉类化合物的一个季氮原子对前三类活性的增强有重要作用。相比之下，四氢异喹啉类盐具有抗hiv活性。(3)小檗碱相关生物碱的杀真菌和除草活性对小檗碱相关的23种季系和叔系原小檗碱进行了体外和体内的杀真菌和除草活性测定。在所检测的化合物中，仅对部分原小檗碱盐有一定的活性，但活性不够强或光谱不够宽，不能用于农化用途。从结构-活动的角度来看，可以指出一些特征。研究了1-苄基四氢异喹啉类化合物在延胡索细胞中的生物转化。采用LC/MS和LC/NMR技术鉴定代谢物。这些技术使我们能够快速分配这些代谢物的结构，同时避免分离单个化合物。发现部分代谢产物为新的2,3,10,11氧合原小檗碱。少

1. Biological Activity of Isoquinoline Alkaloids(1) Cytotoxicity of the Protoberberine-Type AlkaloidsCytotoxic activities of twenty four quaternary protoberberine alkaloids related to berberine have been evaluated using a human cancer cell line panel coupled with a drug sensitivity database. Extending the alkyl chain at position 8 or 13 strongly influenced the cytotoxic activity, that is, relative lipophilicity as well as the size of the substituent affects cytotoxicity. The highest level of activity was observed in 8- or 13-hexyl substituted derivatives of berberine.(2) Biological Activity of Simple Isoquinoline and Benzylisoquinoline AlkaloidsTwenty-six simple isoquinolines and 21 benzylisoquinolines were tested for antimicrobial, antimalarial, cytotoxic, and anti-HIV activities. Some simple isoquinoline alkaloids significantly active in each assay, and may be useful as lead compounds for developing potential chemotherapeutic agents. A quatemary nitrogen atom of isoquinolinium type m … More ay contribute to enhanced potency in the first three types activities. In contrast, anti-HIV activity was found with tetrahydroisoquinoline-type salts.(3) Fungicidal and Herbicidal Activities of Berberine Related AlkaloidsThe 23 quaternary and tertiary protoberberines related to berberine were tested for in vitro and/or in vivo fungicidal and herbicidal activities. Among the compounds tested, there was some activity observed with some of only the protoberberiniumsalts, but not sufficiently strong or broad spectrum for agrochemical utility. From the structure-activity point of view, some features can be pointed out.2. Structural Analysis of Alkaloid Metabolites in Cell Culture of Corydalis Species by LC/NMR and LC/MSThe biotransformations of 1-benzyltetrahydroisoquinolines in the cultured cells of Corydalis species were studied. Identification of metabolites was performed using LC/MS and LC/NMR techniques. These techniques enabled us to assign rapidly structures to these metabolites while avoiding the isolation of individual compounds. It was found that some metabolites were new 2, 3, 10, 11-oxygenated protoberberines. Less